The Principal Investigator has isolated a new hormone-like peptide called chymodenin from porcine duodenum which exhibits a unique biological activity: the selective and perhaps exclusive enhancement of chymotrypsinogen secretion relative to other digestive enzymes by the pancreas. Chymodenin produces a dramatic increase in chymotrypsinogen secretion by the pancreas; this increase is accompanied in non-parallel fashion by a modest increase in total protein output, and no increase in the basal lipase output rate. Chymodenin's effects are unique in that other pancreatic secretory stimulants give a massive increase in the output of pancreatic proteins. Since chymodenin's effect does not appear to be due solely to increased enzyme synthesis because of the rapid response, and since the secretion does not contain elevated levels of all enzymes, the secretory mechanism appears to be unique and distinct from "exocytosis". The broad objectives of this proposal are to study chymodenin's hormonal status - is it a new gastrointestinal hormone? - and to examine in detail its mechanism of action. We will determine its amino acid sequence, develop a radioimmunoassay for the new molecule, and investigate its release from the intestinal wall using the radioimmunoassay to follow its secretion into the blood stream. Chymodenin's mechanism of action on the acinar cell will be studied using pulse-labeling of specific secreted proteins, particularly ChTg, followed by cell fractionation to trace the chymodenin-stimulated secretory route through selected compartments of the cell.